This study applied direct-contact ultrasound-assisted Vacuum Far-Infrared (VFIR) to dry Cistanche slices, investigating the influence of radiation temperature (45 °C, 55 °C, 65 °C), ultrasonic frequency (20 kHz, 40 kHz, 60 kHz) and ultrasonic power (72 W, 96 W, 120 W) on the physicochemical properties, drying characteristics, and microstructure of Cistanche slices. The results showed that the application of ultrasound had a significant enhancement effect on the drying process, with drying time decreasing as radiation temperature, ultrasonic power, and ultrasonic frequency increased. The drying rate curves under three experimental factors exhibited a brief acceleration stage followed by a deceleration stage. Under different drying conditions, the contents of Iridoid and phenylethanoid glycosides in dried products were higher than those under natural drying (ND). Specifically, the content of catalpol at 55 °C, 96 W, 40 kHz (0.56 mg/g) and the content of Leonuride at 55 °C, 96 W, 60 kHz (0.67 mg/g) increased by 1.81 and 1.9 times, compared to ND. The rest of the nutrient content and antioxidant activity increased with the increase in ultrasonic frequency. Compared to ND, ultrasonic-assisted VFIR drying improved the color and rehydration capacity of dried products. Observation of the microstructure revealed that the application of ultrasound made the interior of Cistanche slices loose and porous. In summary, ultrasonic-assisted VFIR drying not only enhances the drying rate but also improves the quality of dried products.